Ticks, and other blood-feeding arthropod vectors, manipulate host homeostatic responses by secreting molecules from their multifunctional salivary glands. In their quest for a blood meal, ticks, and other blood-feeding arthropod vectors, transmit pathogens to their vertebrate hosts. Rickettsiosis is a great example of vector-borne diseases whose importance in public health is underappreciated. Understanding the interactions between vector and pathogen might help in developing strategies to combat arthropod-borne infections. Moreover, characterizing those tick proteins critical for feeding and transmission is essential to developing a molecular basis for new vaccines and therapeutics against tick-borne pathogens. Tick proteins that influence successful Spotted Fever Group Rickettsia (SFGR) infection represent potential candidates for vaccine and/or drug development. Our long-term goal is to reduce the spreading of vector- borne rickettsial disease by interfering with vector proteins. The overall objective of this R15 grant application is to elucidate the biological functin of newly identified selenoproteins in tick physiology and Spotted Fever Group Rickettsia (SFGR) transmission. In this application, we will test our central hypothesis that tick antioxidant factor (Selenoproteins) play an important physiological role by preventing oxidative stress during blood-feeding and protects invading rickettsial agents. This hypothesis will be tested by pursuing the following specific aims using a combination of biochemical, physiological, genetic and cell biological studies. 1) Investigate the physiological function of Amblyomma Selenoproteins in tick feeding success by preventing oxidative stress and inflammation, 2) Disrupt the oxidative balance in the tick to evaluate the tick feeding success and a novel Spotted Fever Group Rickettsia (SFGR) transmission to the host. The proposed work is innovative because the vector-borne pathogens are susceptible to oxidative stress; interference with redox metabolism represents a promising strategy for preventing tick-borne diseases. Results from this R15 research project are expected to demonstrate whether depletion of antioxidant factors in the tick saliva provide a new mechanism to eliminate the SFGR in tick vectors. PUBLIC HEALTH RELEVANCE: The proposed studies are important because they represent an approach to understanding significant tick vector/rickettsial interactions that contribute to rickettsial transmission potential with applicability to all Rickettsia/vector interactions. The proposed research is relevant to protecting public health because understanding spotted fever group rickettsia transmission could enhance research aimed at blocking Rickettsial transmission.